The development of new drugs, formulations and other systems for administration of physiologically active peptides and proteins and other therapeutics and materials is driven by the need to provide these peptides or proteins or other materials to achieve the desirable physiological effects. With respect to peptides and proteins, many of them have been observed to be unstable in the gastro-intestinal tract and therefore may need to be stabilized or protected or delivered via systemic circulation. In addition, peptides and proteins that have low molecular masses tend to have short biological half-lives due to their efficient removal from systemic circulation via kidneys and reticuloendothelial system. Many peptides and proteins can also lose their activity in vivo due to proteolysis (peptide bond cleavage).
In part to circumvent these undesirable effects, a drug delivery system may be used. Drug delivery strategies have been developed for peptide and protein delivery in vivo, but most are not useful for sustained delivery. For example, the use of a continuous systemic infusion of drug via a pump is impractical for outpatients requiring high levels of mobility. Infusion has the associated disadvantages of quality of life and potential intravenous (i.v.) line infections. The use of an implantable pump, comprised of a capsule with a membrane allowing diffusion of a drug, is limited by the volume of the capsule. Peptides and proteins are often used in concentrated formulations in the capsules and aggregate, whereby losing specific activity. In many cases, the drug is released into the extracellular space and distributed in lymphatics. Other implantable biodegradable delivery systems are implanted or injected into the epidermis. The components of the system are usually slowly degraded as a result of biological activity of surrounding cells (i.e. as a result of the release of enzymes degrading chemical bonds that hold these implants together).
Proteins that have a net positive charge in their surface under physiological conditions and have basic (greater than pH 7.5) isoelectric point (pI) will benefit from the composition of the present invention. The use of basic proteins has much therapeutic potential, including uses in treating cancer and related neoplastic diseases, systemic infections, inflammations, and diseases of the nervous system such as Alzheimer's disease, Parkinson's disease, and prion diseases. There is a need for a biodegradable drug delivery carrier for the systemic delivery of basic (pI greater than pH 7.5) proteins and peptides that will provide longer circulation in the body, more stability in the blood, and can be more conveniently administered. In one embodiment of the present invention the anti-infective agent that benefits from the carrier of the present invention is lysostaphin with pI of 9.56. Most peptides and drugs that can potentially be useful in vivo in blocking specific intracellular mechanism requires basic moieties such as amino groups that allow membrane internalization. By attaching basic residues, these intracellular acting peptides and drugs can penetrate biological membranes. These basic residues are sometimes referred collectively as cell penetrating moiety or cell penetrating peptides (Cell-Penetrating Peptides by Ulo Langel, Pharmacology & Toxicology Series, 2002, CRC Press, New York).